Microfluidic elements for analyzing a liquid sample and for blending a liquid with a reagent are used in diagnostic tests (in vitro diagnostics). In these tests, bodily fluid samples are determined for an analyte contained therein for medical purposes. The term blending comprises the possibility that the reagent is provided in liquid form, i.e., that two liquids are mixed with one another. In addition, the term comprises the possibility that the reagent is provided as a solid and is dissolved in a liquid and homogenized. In many applications, the solid dry reagent is introduced in liquid form into the fluidic element and dried in a further step, before the element is used for the analysis.
An important component during the analysis are test carriers, on which microfluidic elements having channel structures for accommodating a liquid sample are provided, to allow the performance of complex and multistep test protocols. A test carrier can comprise one or more fluidic elements.
Test carriers and fluidic elements consist of a carrier material, typically a substrate made of plastic material. Suitable materials are, for example, COC (cyclo-olefin copolymers) or plastics such as PMMA, polycarbonate, or polystyrene. The test carriers have a sample analysis channel, which is enclosed by the substrate and a cover or a cover layer. The sample analysis channel frequently consists of a succession of a plurality of channel sections and interposed chambers, which are expanded in comparison to the channel sections. The structures and dimensions of the sample analysis channel having its chambers and sections are defined by a structuring of plastic parts of the substrate, which is generated by injection-molding technologies or other methods for producing suitable structures, for example. It is also possible to introduce the structure by material-removing methods such as milling.
Fluidic test carriers are used, for example, in immunochemical analyses having a multistep test sequence, in which a separation of bound and free reaction components occurs. A controlled liquid transport is required for this purpose. The control of the process sequence can be performed using internal measures (inside the fluidic element) or using external measures (outside the fluidic element). The control can be based on the application of pressure differences or also the change of forces, for example, resulting from the change of the action direction of gravity. If centrifugal forces occur, which act on a rotating test carrier, a control can be performed by changing the rotational velocity or the rotational direction or through the spacing from the rotational axis.
To perform the analyses, the sample analysis channel of the microfluidic elements contains at least one reagent, which reacts with a liquid introduced into the channel. The liquid and the reagent are mixed with one another in the test carrier so that a reaction of the sample liquid with the reagent results in a change of a measuring variable which is characteristic for the analyte contained in the liquid. The measuring variable is measured on the test carrier itself. Measurement methods which can be optically evaluated and in which a color change or another optically measurable variable is detected, are typical.
For the performance of the analysis, it is decisive that the reagent provided in dried form is dissolved by the sample liquid and is blended therewith. In the prior art, some efforts have been made to improve the blending. For example, in rotating test carriers, which are rotated around a rotational axis in an analysis system, the blending is promoted by rapid changes of the rotational direction. This resulting “shake mode” is described, for example, in a particular embodiment by Markus Grumann, “Readout of Diagnostic Assays on a Centrifugal Microfluidic Platform”, (Dissertation University of Freiburg, 2005, URN (NBN): urn:nbn:de:bsz:25-opus-22723).
Further known methods for improving the blending of sample liquid and reagent comprise the introduction of magnetic particles, which are set into motion by the action of an electromagnet or permanent magnet. The outlay during the production of the test carriers rises through the integration of the particles. In addition, the analysis systems must have further components, namely the magnets, and therefore become expensive.
Other methods include, for example, elements whose capillary channels contain particular flow obstructions. The production of such obstructions, for example, ribs, must be implemented in the microstructure and are therefore expensive and make the production process of the test carrier more difficult. In addition, such structures are not suitable for all mixing processes or for all reagents and sample liquids.
In spite of the manifold efforts to improve mixing procedures in microfluidic elements, in particular the blending of dried solid reagents and sample liquids, there is still a demand for a microfluidic element or test carrier, in which the blending of small amounts of sample liquids in particular is improved. Furthermore, the fluidic element is to be capable of simultaneously dissolving different reagents which are introduced separately and are located at different spatial locations, for example, and to cause the sample liquid to react with different reagents.